chapter 5: non-opioid analgesics

what is pain?

when the CNS gets signals of impending tissue damage

what is pain sensation?

the physical sensory feelings of pain

what is pain as suffering?

pain sensation and emotional reactions

what is the purpose of pain?

protective mechanism for survival, indicates underlying conditions

what is allogynia?

pain from non-injurious stimuli

what is hyperalgesia?

extreme sensitivity to pain

what is analgesia?

absence of pain from normally painful stimuli

where is the site of action for non-opioids?

peripheral nerve endings

where is the site of action for opioids?

CNS

what is the mechanism of action for non-opioids?

inhibits prostaglandin synthesis through COX inhibition

what is the mechanism of action for opioids?

CNS depression

what is CNS depression?

when CNS activity slows down

what are examples of non-opioids?

aspirin, NSAIDs, acetaminophen

what are examples of opioids?

morphine, codeine, oxycodone

why is acetaminophen not a NSAID?

analgesic and antipyretic but NOT anti-inflammatory

what does NSAID stand for?

non-steroidal anti-inflammatory drug

what is the mechanism of action of NSAIDs?

inhibits COX enzymes and reduces prostaglandin synthesis

what do COX enzymes do?

synthesize prostaglandins

what do prostaglandins do?

1. sensitize pain receptors/lower pain threshold

2. causes inflammation and fever

3. affects vascular tone and permeability

4. protects GI lining

5. increases smooth muscle contraction

how do prostaglandins protect GI lining?

stimulates mucus and bicarbonate production

what does COX-1 do?

produces prostaglandins that protect stomach lining and support platelet functions

what is COX-2 associated with?

prostaglandin production during inflammation and pain

do NSAIDs reversibly or irreversibly inhibit COX-1 and -2?

reversibly

what is the exception to NSAIDs reversibly inhibiting COX-1 and -2?

aspirin, irreversibly inhibits both

what are the effects of aspirin?

1. analgesic

2. antipyretic

3. anti-inflammatory

4. anti-platelet

5. worsens gout

how does aspirin affect gout?

increases uric acid that trigger joint flare-ups

what do platelets use COX-1 for?

producing thromboxanes

what do thromboxanes promote?

clotting

what is the life cycle of a platelet?

8-12 days

what are adverse effects of aspirin?

1. can irritate stomach lining

2. increases susceptibility to acid-related injury

3. increased bleeding time/risk

what is the absorption like for aspirin?

rapid absorption from stomach and small intestine

what reduces rate of aspirin absorption?

food

what is the distribution for aspirin?

widely distributed

what is metabolism like for aspirin?

metabolized to salicylate in GI tract through hepatic first pass

what is the excretion of aspirin?

urine

what happens when aspirin is combined with anticoagulants?

increased bleeding risk, contraindication

what happens when aspirin is combined with alcohol?

increased GI bleeding and gastric irritation

what happens when aspirin is combined with gout medication?

decreased urid acid clearance and may counteract gout treatment

what happens when aspirin is combined with sulfonylureas?

enhances hypoglycemic effects

what is the glycemic index?

measures how fast a carb containing food raised blood sugar levels compared to pure glucose

what happens when aspirin is combined with other NSAIDs?

NSAIDs may interfere with aspirin’s anti-platelet effects

what are examples of non-acetylated salicylates?

1. sodium salicylate

2. magnesium salicylate

3. salsalate

4. salicylamide

what are important characteristics of non-acetylated salicylates?

1. close in efficacy to aspirin for pain, joint tenderness, and inflammation

2. safer for GI bleeding and clotting

3. not anti-pyretic

what are examples of common NSAIDs?

1. ibuprofen

2. naproxen

3. diclofenac

what is the drug of choice for dental pain?

ibuprofen

what is naproxen?

similar to ibuprofen but higher incidence of GI bleeding

what are examples of ibuprofen?

advil, motrin

what are examples of naproxen?

aleve, anaprox

what are uses of NSAIDs?

1. osteoarthritis/rheumatoid arthritis

2. gout arthritis

3. fever and pain

what are GI adverse effects for NSAIDs?

irritation, pain, ulcers, bleeding

what are renal adverse effects for NSAIDs?

decreased renal blood flow and increased fluid retention

what are bleeding adverse effects for NSAIDs?

reversible inhibition of platelet aggregation

what are CNS adverse effects for NSAIDs?

dizziness, sedation, confusion, headache, vertigo

what is vertigo?

false sensation of spinning

what are hypersensitivity adverse effects for NSAIDs?

hives, itching, fever, angioedema

what is angioedema?

swelling under skin or mucous membranes

what are cardiovascular adverse effects for NSAIDs?

increased risk of MI and stroke

what are oral adverse effects for NSAIDs?

ulcerative stomatitis, gingival ulcers, xerostomia

what is ulcerative stomatitis?

disease causing painful sores and erosions in mouth

what may NSAIDs increase effects/toxicity of?

1. lithium

2. methotrexate

3. digoxin

4. anti-gout medication

what may NSAIDs decrease the effects of?

1. ACE inhibitors, diuretics, and beta blockers

   1. aspirin’s anti-platelet effect

is acetaminophen an NSAID?

no

what are the uses for acetaminophen?

1. analgesia

2. anti-pyretic

3. not significantly anti-inflammatory

what is acetaminophen equally effect to?

aspirin

what is acetaminophen preferred for?

1. patients allergic to aspirin

2. patients with bleeding disorders

3. patients with GI problems

4. children

what is the absorption of acetaminophen?

orally

where is acetaminophen metabolized?

liver

how is acetaminophen excreted?

urine

what does acetaminophen produce when metabolized?

NAPQI

what is NAPQI?

toxic metabolite responsible for acetaminophen related liver injury

what is the maximum daily dose of acetaminophen?

4g

what is the overdose threshold of acetaminophen?

7.5g

what is treatment for toxic doses of acetaminophen?

1. gastric lavage

2. activated charcoal

3. oral N-acetylcysteine (antidote)

what are adverse effects of acetaminophen?

1. nephrotoxicity with long term consumption

2. 
   

what is nephrotoxicity?

toxic damage to kidneys

what is gout?

inflammatory form of arthritis

what causes gout?

excess uric acid

what does uric acid do in gout?

crystallizes and deposits in joints, causing pain and swelling

what is rheumatoid arthritis?

chronic, systemic, inflammatory disorder involving synovial joints

what causes RA?

unknown etiology

what is the goal of treating RA?

control inflammatory response in synovial fluid

what are the 2 methods of treating RA?

1. NSAIDs/corticosteroids

2. disease modifying anti-rheumatic drugs (DMARDs)

what do NSAIDs/corticosteroids do for RA?

1. relieves pain

2. temporary relief

3. does not stop disease progression

what do DMARDs do for RA?

1. suppresses immune and inflammatory responses

2. slows/stops RA progression

3. preserves joint integrity/function

what is methotrexate used in?

many combination therapies for RA and psoriasis

what is methotrexate?

non-biologic DMARD; competitive antagonist of an enzyme for purine synthesis

what does methotrexate do?

1. inhibits DNA and protein synthesis in activated T cells

2. reduces inflammatory mediators (like TNF-α)

what are adverse effects of methotrexate?

1. immunosuppression

2. GI upset

3. mouth ulcers/sores

4. headache and fatigue

what are contraindications for methotrexate?

1. pregnancy

2. chronic infection/TB

3. liver/kidney damage

what drug interaction should methotrexate be checked for?

NSAIDs - interferes with methotrexate’s renal clearance, may increase toxicity